Phase 1-2 Study of ASTX660 in Subjects With Advanced Solid Tumors and Lymphomas

NCT02503423 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: ASTX660-012016-005039-34HC6-24-c206781
• Study Type: interventional
• Target: 253
• Locations: 8 countries
• Sites: 68

Brief Summary

This is an open-label, dose-escalation Phase 1/2 study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and recommended dosing regimen, and to obtain preliminary efficacy, pharmacokinetic (PK), and target engagement data, in subjects with advanced solid tumors or lymphoma for whom standard life-prolonging measures are not available.

Conditions

Solid Tumors; Lymphoma

Keywords

cervical cancer; HNSCC; CTCL; PTCL; DLBCL

Outcome Measures

Primary Outcomes (3)

• Safety (Phase 1) - number of subjects with AEs, DLTs, abnormal clinical laboratory values or physical exam results

  Incidence of dose-limiting toxicities (DLTs) and other adverse events (AEs)

  Up to 78 months

• Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR)

  Antitumor activity by objective response rate

  Up to 84 months

• Efficacy (Phase 2) - antitumor activity assessed by disease control rate (DCR)

  Antitumor activity by disease control rate

  Up to 84 months

Secondary Outcomes (11)

• Pharmacokinetic outcome of concentration-time curve (AUC)

  First 9 weeks of study treatment

• Pharmacokinetic outcome of maximum concentration (Cmax)

  First 9 weeks of study treatment

• Pharmacokinetic outcome of minimum concentration (Cmin)

  First 9 weeks of study treatment

• Pharmacokinetic outcome of time to maximum concentration (Tmax)

  First 9 weeks of study treatment

• Pharmacokinetic outcome of samples over time

  First 9 weeks of study treatment

Study Arms (9)

Phase 1 - Part 1 (completed)

EXPERIMENTAL

Dose-escalation stage to identify the MTD and the RP2D, defined as either the MTD or a dose below the MTD that the Data and Safety Review Committee (DSRC) agree shows adequate pharmacological evidence of target engagement and/or clinical activity. Subjects will receive ASTX660 once a day for 7 consecutive days every other week of each 28-day cycle (ie, \[7 days on/ 7 days off\] ×2; daily dosing on Days 1-7 and 15-21). The starting dose will be escalated stepwise in successive cohorts of 3 to 6 evaluable subjects each (standard 3+3 study design), until the RP2D is determined.

Drug: ASTX660

Phase 1 - Part 2 (completed)

EXPERIMENTAL

Dose-expansion stage to confirm tolerability of ASTX660 at the RP2D using the every-other-week daily dosing regimen. Up to a total of 12 subjects (including the 3 or 6 subjects treated at the RP2D in Part 1) will be treated at the RP2D.

Drug: ASTX660

Phase 1 - Part 3 (optional)

EXPERIMENTAL

The purpose of the optional Part 3 is to allow for exploration of an alternative dosing regimen of ASTX660 based on emerging safety, PK, and pharmacodynamic (PD) data from Parts 1 and 2 (using the original every-other-week dosing regimen), with agreement of the DSRC. If Part 3 is conducted, the plan is to enroll up to 18 evaluable subjects in 1 or more cohorts using a standard 3+3 study design.

Drug: ASTX660

Phase 2 - Cohort 1

EXPERIMENTAL

Treatment with ASTX660 for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) not responsive or relapsed after standard therapy.

Drug: ASTX660

Phase 2 - Cohort 2

EXPERIMENTAL

Treatment with ASTX660 for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Drug: ASTX660

Phase 2 - Cohort 3

EXPERIMENTAL

Treatment with ASTX660 for progressive or relapsed peripheral T-cell lymphoma (PTCL).

Drug: ASTX660

Phase 2 - Cohort 4

EXPERIMENTAL

Treatment with ASTX660 for relapsed or refractory cutaneous T-cell lymphoma (CTCL).

Drug: ASTX660

Phase 2 - Cohort 5

EXPERIMENTAL

Treatment with ASTX660 for other tumor types that are characterized by a molecular feature that may confer sensitivity to ASTX660 (eg, oncogenic activation of the NF-κB pathway or documented amplification of the gene loci encoding c-IAP1 or c-IAP2), pending confirmation in writing by the Astex medical monitor.

Drug: ASTX660

Phase 2 - Cohort 6

EXPERIMENTAL

Treatment with ASTX660 for cervical carcinoma not responsive or relapsed after standard therapy.

Drug: ASTX660

Interventions

ASTX660 DRUG

described above

Also known as: Treatment of ASTX660 for advanced solid tumors and lymphomas

Phase 1 - Part 1 (completed); Phase 1 - Part 2 (completed); Phase 1 - Part 3 (optional); Phase 2 - Cohort 1; Phase 2 - Cohort 2; Phase 2 - Cohort 3; Phase 2 - Cohort 4; Phase 2 - Cohort 5; Phase 2 - Cohort 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and comply with the protocol and study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
• Men and women 18 years of age or older.
• Participants with histologically or cytologically confirmed advanced solid tumors or lymphoma that is metastatic or unresectable, and for whom standard life-prolonging measures are not available. Specific tumor types that will be selected for study in Phase 2 are detailed in the protocol.
• a. For Phase 2 Cohort 3, participants must have histologically confirmed PTCL (local pathology report) as defined by 2016 World Health Organization (WHO) classification. The following subtypes are eligible for the study: adult T-cell lymphoma/leukemia, extranodal natural killer (NK)/T-cell lymphoma nasal type, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, nodal peripheral T-cell with T-follicular helper (THF) phenotype, and anaplastic large-cell lymphoma.
• For Phase 2 Cohorts 3 and 4, participants must have evidence of documented progressive disease and must have received at least two prior systemic therapies.
• Participants with CD30-positive lymphoma must have received, be ineligible for, or intolerant to brentuximab vedotin, provided that brentuximab vedotin is locally approved and available.
• Participants with mycosis fungoides or Sezary syndrome must have received, be ineligible or intolerant to mogamulizumab, provided that mogamulizumab is locally approved and available.
• In the Phase 2 portion of the protocol only, participants must have measurable disease according to response criteria appropriate for their type of cancer.
• a. For Phase 2 Cohort 3 (PTCL), measurable disease by contrast-enhanced diagnostic CT (at least 1 nodal lesion \>1.5 cm or extranodal lesions \>1.0 cm) is required.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Acceptable organ function, as evidenced by the following laboratory data:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=2.0 \* upper limit of normal (ULN).
• Total serum bilirubin \<=1.5 \* ULN
• Absolute neutrophil count (ANC):
• Phase 1 and 2 (except Phase 2 participants with known lymphoma; ie, not applicable for Cohorts 3 or 4) \>=1500 cells/mm3

You may not qualify if:

• Hypersensitivity to ASTX660, excipients of the drug product, or other components of the study treatment regimen.
• Poor medical risk because of systemic diseases (e.g. active uncontrolled infections) in addition to the qualifying disease under study.
• Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise participant safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of ASTX660.
• History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
• Abnormal left ventricular ejection fraction (LVEF; \<50%) or echocardiogram ECHO or multiple gated acquisition scan (MUGA).
• Congestive cardiac failure of \>= Grade 3 severity according to New York Heart Association (NYHA) functional classification defined as participants with marked limitation of activity and who are comfortable only at rest.
• Unstable cardiac disease including angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
• History or presence of complete left bundle branch block, heart block, cardiac pacemaker or significant arrhythmia.
• Concurrent treatment with any medical that prolongs QT interval and may induce torsades de pointes, and which cannot be discontinued at least 2 weeks before treatment with ASTX660. \[Applies to Phase 1 only\].
• Personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
• Screening 12-lead ECG with measurable QTc interval (according to either Fridericia's or Bazett's correction) of \>=470 msec).
• Any other condition that, in the opinion of the investigator, could put the participant at increased cardiac risk.
• Known history of human immunodeficiency virus (HIV) infection, or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
• Grade 2 or greater neuropathy \[Applies to Phase 1\]. Grade 3 or greater neuropathy \[Applies to Phase 2\].
• Known brain metastases, unless stable or previously treated.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (68)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

HonorHealth Research Institute

Scottsdale, Arizona, 852558, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Simlow Cancer Hospital at Yale

New Haven, Connecticut, 06510, United States

Location

Emory University winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Dartmouth-Hitchcock Medical Center (DHMC)

Lebanon, New Hampshire, 03766, United States

Location

Summit Medical Group - Florham Park Campus/Atlantic Health

Florham Park, New Jersey, 07932, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

New York Presbyterian Hospital Columbia University Medical Center

New York, New York, 10019, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Rochester Skin Lymphoma Medical Group

Rochester, New York, 14450, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University and Wexner Medical Center, James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37212, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

CliniCore Texas

Houston, Texas, 77079, United States

Location

START- South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Virgina Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Washington, Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne

Yvoir, Namur, B-5530, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Intitut Jules Boredt

Brussels, 1000, Belgium

Location

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Cancer Care Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Nova Scotia Health Athority-Qeii HSC

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Sunnybrook Hospital

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M56 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Gustave Roussy Cancer Campus (IGR)

Villejuif, Cedex, 94805, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Lyon, 69310, France

Location

Institut Bergonié, Unicancer

Bordeaux, 33000, France

Location

Centre Antoine Lacassagne, Oncologie Médicale

Nice, 06189, France

Location

Centre Henri Becquerel, Hematology

Rouen, 1,76-38, France

Location

Institut Universitaire du Cancer - Oncopôle, Department d'Hématologie

Toulouse, 31059, France

Location

CRU de Tours - Hôpital Bretonneau, Hématologie -Thérapy Cellulaire

Tours, 37044, France

Location

Semmelweis Egyetem - I. sz. Belgyógyászati Klinika

Budapest, 1083, Hungary

Location

Debreceni Egyetem Klinikai Központ

Debrecen, 4032, Hungary

Location

Szabolcs-Szatmár-Bereg Megyei Kórházak És Egyetemi Oktatókórház

Nyíregyháza, Hungary

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Instituto Europeo di Oncologia

Milan, Italy

Location

Azienda Socio Santaria Territoriale Monza- Osperdale San Gerado

Monza, Italy

Location

Institut Catala d'Oncologia

Girona, Giona, Spain

Location

imCORE - Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz Preview

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

University Hospitals of Leicester NHS Trust

Leicester, East Midlands, LE1 5WW, United Kingdom

Location

University Hospital Southhampton NHS Foundation Trust - Somers Cancer Research

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Churchill Hospital, Oxford University Hospital NHS Trust

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Beatson Cancer Center and University of Glasgow

Glasgow, G12 0XL, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

Guy's and Saint Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

The Christie NHS Foundation Trust, Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Johnson CN, Ahn JS, Buck IM, Chiarparin E, Day JEH, Hopkins A, Howard S, Lewis EJ, Martins V, Millemaggi A, Munck JM, Page LW, Peakman T, Reader M, Rich SJ, Saxty G, Smyth T, Thompson NT, Ward GA, Williams PA, Wilsher NE, Chessari G. A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1 H,2 H,3 H-pyrrolo[3,2- b]pyridin-1-yl)-2-[(2 R,5 R)-5-methyl-2-([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660). J Med Chem. 2018 Aug 23;61(16):7314-7329. doi: 10.1021/acs.jmedchem.8b00900. Epub 2018 Aug 9.

  PMID: 30091600 DERIVED

MeSH Terms

Conditions

Lymphoma; Uterine Cervical Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

ASTX-660

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2015
• First Posted: July 21, 2015
• Study Start: July 14, 2015
• Primary Completion: October 1, 2022
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-03

Locations

ES (4); BE (3); FR (7); HU (3); IT (4); GB (9); US (31); CA (7)